DESCRIPTION (provided by investigator): There is a continuing need for new antimicrobial agents. Pinnacle Pharmaceuticals proposes a genomically-based strategy for the identification of compounds that potentiate the action of known antibiotics. In preliminary experiments, Pinnacle scientists have identified a physiological function that is metabolically related to a known aminoglycoside antibiotic. These observations lead to the hypothesis that targeting this function will lead to compounds that potentiate known aminoglycoside antibiotics. The specific aims of the present application are to (1) carry out high-throughput screening to identify these potentiating compounds and to identify the active principles and (2) to characterize the action of these compounds against wild-type cells, clinically relevant R-determinants, and pathogenic bacteria.